Ototoxicity of topical azithromycin solutions in the guinea pig.
ABSTRACT To investigate possible ototoxic effects of topical azithromycin (AZ) in the guinea pig.
A prospective, controlled animal study.
The University of Texas Southwestern Medical Center at Dallas.
Twenty-three pigmented guinea pigs were given single, unilateral middle ear applications of a solution containing 3% (n = 3), 2% (n = 5), 1% (n = 5), or 0.5% (n = 5) AZ or saline (n = 5). The contralateral ear served as the untreated control.
The animals were observed for behavioral changes for 2 weeks and then humanely killed. The ears were processed for anatomical evaluation. Morphologic changes were analyzed by quantitation of middle ear changes and cochlear inner and outer hair cell loss. Statistical analysis was performed to examine effects by dose.
Analysis revealed extensive middle and inner ear changes associated with all formulations of AZ. Moderate correlation was found between the extent of middle ear changes and AZ concentration (r(2) = 0.59), whereas a strong correlation was seen between inner ear damage and AZ concentration (r(2) = 0.94). Both inner and outer hair cells were affected, with inner hair cell damage consistently greater than outer hair cell damage.
The results of this study demonstrate that ototopical AZ can cause middle ear changes and significant hair cell loss in the guinea pig. This finding, together with previous clinical reports, indicates that topical AZ should be used with caution in the clinical setting.
SourceAvailable from: Hirohi Hidaka[Show abstract] [Hide abstract]
ABSTRACT: Objectives. Recent advances in endoscopic technology have allowed its application to middle ear surgery. An antifog agent is necessary for endoscopy because moisture and blood may obscure visibility. Ultrastop is one of the most commonly used antifog agents. The current study examined the ototoxic effect of topical application of Ultrastop in the guinea pig ear. Study Design. A preliminary experimental animal study. Setting. University hospital. Subjects and Methods. Eighteen male Hartley guinea pigs (weight, 480-620 g) were divided into 3 groups to be treated with Ultrastop, gentamicin (50 mg/mL, positive control), or saline solution (negative control). After auditory brainstem responses were measured, topical solutions of 0.2 mL were applied through a small hole made at the tympanic bulla. Posttreatment auditory brainstem responses were obtained 14 days after the treatment. The extent of middle ear damage was investigated and scored. Results. The saline-treated group showed no deterioration in auditory brainstem response threshold. The Ultrastop-treated and gentamicin-treated groups showed severe deterioration in auditory brainstem response threshold. Middle ear examination revealed extensive changes in the Ultrastop-treated group and medium changes in the gentamicin-treated group. Conclusion. Ultrastop applied topically to the guinea pig middle ear caused significant middle ear inflammation and hearing impairment.Otolaryngology Head and Neck Surgery 08/2014; 151(1 Suppl). DOI:10.1177/0194599814545749 · 1.72 Impact Factor
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ABSTRACT: INTRODUCTION: Drug ototoxicity represents one of the main preventable causes of deafness. Ototoxicity is a trait shared by aminoglycoside and macrolide antibiotics, antimalarial medications, loop diuretics, platinum-based chemotherapeutic agents, some NSAIDs and most recently described, acetaminophen when abused with narcotic medication. These medications are prescribed despite their side effects, which includes inner ear toxicity, because they are life-saving drugs or there is a lack of better treatment. AREAS COVERED: This review will discuss in vitro and in vivo models of ototoxicity highlighting recently published ototoxicity research. The reader will learn the strengths and limitations of different ototoxicity models and what molecular insights have been gained from their application. A better understanding of the cellular mechanisms of these ototoxins will help in the discovery of ways to prevent and treat hearing loss associated with ototoxic medications. EXPERT OPINION: There are benefits to both in vitro and in vivo models of ototoxicity. Research of a particular medication and its ototoxic mechanisms should draw from several models, enabling a better answer to the clinical question of prevention and treatment of inner ear drug toxicity.Expert Opinion on Drug Metabolism & Toxicology 12/2011; 7(12):1521-34. DOI:10.1517/17425255.2011.614231 · 2.94 Impact Factor
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ABSTRACT: HYPOTHESIS: Repeated applications of low-concentration povidone iodine (PI) combined with dexamethasone (Dex) through a tympanic membrane ventilation tube will not cause ototoxic changes in the rat. BACKGROUND: Otitis externa (OE) and acute otitis media (AOM) are 2 of the most common otologic disorders requiring outpatient antibiotic treatment. The development of topical treatments that are easy to administer would help to limit systemic exposure to antibiotics in these patients. Topical formulations containing Dex and low-dose PI were designed to provide both antimicrobial and anti-inflammatory effects for the treatment of OE and AOM. Treatment with PI alone has shown mixed results in studies designed to determine PI. Low concentrations of PI combined with Dex should yield less ototoxicity while maintaining effectiveness. METHODS: We performed tympanostomies on rats, inserting a ventilation tube to administer 1% or 2% PI, plus 0.1% Dex over a period of 7 days. Hearing was accessed via auditory brainstem response (ABR) testing over the duration of the study and histologic analysis was performed 15 days after the initial application to determine the effect of administration of PI/Dex on middle and inner ear structures. CONCLUSION: The preparations used in the present investigation were formulated to allow repeated applications to both the external and middle ear, without risk to hearing or equilibrium. Neither of the PI/Dex formulations tested caused pathologic changes in the ear that significantly affected equilibrium, hearing function or morphology.Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 11/2012; 34(1). DOI:10.1097/MAO.0b013e31827a21a2 · 1.44 Impact Factor